This K01 application seeks support essential to my development as an independent interdisciplinary scientist. I am building a program of biopsychosocial research on self-regulation; particularly affect reduction and negative reinforcement (NR) as they relate to the development of substance use in adolescence. I have employed behavioral, electrophysiological, and hormonal assays (cortisol) to study risk-taking behavior. However, to fully understand avoidance and negative reinforcement processes, and their role in the risk for addictive behavior, I must deepen my understanding and broaden my technical skills in four core areas (a) developmental neuroimaging; (b) cognitive neuroscience; (c) substance use research; (d) statistical methods. This mentored scientist development award will provide me with the training to move onto an independent research career. While adolescence is a developmental period with increased risk-taking behavior and increased affect reduction motivation, we know relatively little about how the neural correlates of negative reinforcement processes relate to affect reduction motives and substance use behaviors. I address these gaps in our knowledge with three specific aims across two cross-sectional fMRI studies. I propose to study the neural and behavioral correlates of negative reinforcement for avoidance with two types of aversive stimulation (e.g., avoidance of incentive loss and avoidance of aversive sound) across two fMRI-friendly behavioral paradigms. The first study (n=48) will characterize the neural circuitry underlying negative reinforcement processes and behavior among children (8-11 yrs.), adolescents (13-17 yrs.), and adults (23-29 yrs.) The second study will examine the negative reinforcement-related neural correlates of affect reduction motives (negative affect, anxiety sensitivity) and substance use behaviors in a high-risk sample (14-18 yrs., n=70). PUBLIC HEALTH RELEVANCE: At a minimum, this work will address important gaps in the knowledge base regarding adolescent development and the neural correlates of negative reinforcement in adolescence. Drawing on a high-risk sample, this work examines the neural correlates of negative reinforcement as they relate to high-risk behaviors including substance use. In addition to providing basic knowledge, this work also may have more long-range public health implications for the development of more effective and targeted interventions for adolescents at risk for substance use; particularly, those adolescents who turn to substance use or other risky behaviors to cope with aversive negative affect.